Abstract
Selective renal carbonic anhydrase inhibition with full renal HCO3- response may be obtained without respiratory effect of erythrocytic enzyme inhibition during chronic administration of 2-benzenesulfonamido-1,3,4-thiadiazole -5-sulfonamide (CL 11,366) in unanesthetized dogs by appropriate choice of dose and interval. As little as 0.5 mg/kg i.m. gives maximal rates of renal HCO3- loss, and administration every 4 hr approaches maximally sustained plasma HCO3- depletion. As much as 10 mg/kg p.o. every 12 hr fails to bring about respiratory changes characteristic of erythrocytic inhibition. Studies of distribution of CL 11,366 show it to be concentrated in kidney and lung, where it is apparently secreted, and to be low in muscle and brain, from which it is largely excluded because of high plasma binding and poor diffusibility. Exclusion of physiologically effective concentration from erythrocytes is possible because the composite of chemical and pharmacologic factors keep free drug in the red cells at a lower level than the unbound plasma inhibitor concentration, which is small at maximum renal doses.
Footnotes
- Accepted September 24, 1965.
- The Williams & Wilkins Comapny
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|